Methods for quantifying insulin sensitivity and determining insulin time-action profiles

Abstract

Impaired insulin action is a prominent metabolic defect in obese subjects and patients with type 2 diabetes. Reducing obesity through non-pharmacological or pharmacological interventions improves insulin sensitivity. Drugs that directly improve insulin sensitivity, notably biguanides and thiazolidinediones, are widely used in the treatment of patients with type 2 diabetes. The development of new insulin-sensitizing drugs requires robust and reproducible measurement of insulin action. Determining the time-action profiles of insulin formulations that are used for insulin therapy in patients with diabetes by means provides important pharmacodynamic information for optimizing the therapy. The advent of novel insulin delivery systems, e.g. inhaled insulin, adjunctive measures to alter insulin action, and biosimilar insulins, requires assessment of pharmacodynamic properties. The hyperinsulinaemic glucose clamp technique is widely regarded as the reference method for determining the effects of drugs with insulin-sensitizing actions. The euglycaemic glucose clamp technique is widely used to measure the time-action profiles of insulin preparations. However, glucose clamp studies are resource- and labour-intensive. All variants of the glucose clamp technique are to some extent operator dependent.